Using the Sum of Roots and Its Application to a Control Design Problem

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Silkworm Pupae Function as Efficient Producers of Recombinant Glycoproteins with Stable-Isotope Labeling

Baculovirus-infected silkworms are promising bioreactors for producing recombinant glycoproteins, including antibodies. Previously, we developed a method for isotope labeling of glycoproteins for nuclear magnetic resonance (NMR) studies using silkworm larvae reared on an artificial diet containing 15N-labeled yeast crude protein extract. Here, we further develop this method by introducing a technique for the expression of isotope-labeled glycoproteins by silkworm pupae, which has several potential advantages relative to larvae-based techniques in terms of production yield, ease of handling, and storage. Here, we fed fifth instar larvae an artificial diet with an optimized composition containing [methyl-13C]methionine, leading to pupation. Nine-day-old pupae were then injected with recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid for expression of recombinant human immunoglobulin G (IgG). From the whole-body homogenates of pupae, 0.35 mg/pupa of IgG was harvested, which is a yield that is five times higher than can be obtained from larvae. Recombinant IgG, thus prepared, exhibited mainly three kinds of pauci-mannose-type oligosaccharides and had a 13C-enrichment ratio of approximately 80%. This enabled selective observation of NMR signals originating from the methionyl methyl group of IgG, confirming its conformational integrity. These data demonstrate the utility of silkworm pupae as factories for producing recombinant glycoproteins with amino-acid-selective isotope labeling

Cytokine profiles in children with primary Epstein-Barr virus infection

Primary Epstein-Barr virus (EBV) infection causes infectious mononucleosis and hemophagocytic lymphohistiocytosis (HLH) in children, where EBV infects B and CD8+ T cells, respectively. We measured pro-inflammatory and anti-inflammatory cytokines in both diseases. Significantly higher concentrations of various mediators, including interferon-γ, neopterin, interleukin (IL)-6, IL-10, IL-18, and heme oxygenase-1, were observed in EBV-HLH. Because of their similarity to the profile of familial HLH, this profile was likely a consequence of HLH, but not ectopic infection. TNF-α levels were elevated in both diseases. Elevation of those mediators may contribute to the disease pathogenesis of EBV-HLH by activating and inhibiting host immune responses. © 2013 Wiley Periodicals, Inc

Impact of Mild Paravalvular Regurgitation on Long- Term Clinical Outcomes After Transcatheter Aortic Valve Implantation

The impact of mild paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) remains controversial. We evaluated the impact of mild PVR after TAVI on long-term clinical outcomes. We included patients who underwent TAVI for severe symptomatic aortic stenosis between December 2008 and June 2019 at 2 interna-tional centers and compared all-cause death between the group with mild PVR (group 1) and the group with none or trace PVR (group 2). PVR was categorized using a 3-class grading scheme, and patients with PVR >= moderate and those who were lost to follow-up were excluded. This retrospective analysis included 1,404 patients (mean age 81.7 +/- 6.5 years, 58.0% women). Three hundred fifty eight patients (25.5%) were classified into group 1 and 1,046 patients (74.5%) into group 2. At baseline, group 1 was older and had a lower body mass index, worse co-morbidities, and more severe aortic stenosis. To account for these differences, propensity score matching was performed, resulting in 332 matched pairs. Within these matched groups, during a mean follow-up of 3.2 years, group 1 had a significantly lower survival rate at 5 years (group 1: 62.0% vs group 2: 68.0%, log-rank p = 0.029, hazard ratio: 1.41 [95% confidence interval: 1.04 to 1.91]). In the matched cohort, patients with mild PVR had a significant 1.4-fold increased risk of mortality at 5 years after TAVI compared with those with none or trace PVR. Further studies with more patients are needed to evaluate the impact of longer-term outcomes.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) (Am J Cardiol 2023;191:14-22)Peer reviewe

Two types of antigorite serpentinite controlling heterogeneous slow-slip behaviours of slab-mantle interface

It is known that plate boundaries in subduction zones show heterogeneous slip nature with strongly coupled seismogenic zones and various types of episodic tremor and slip (ETS) zones. In order to examine the petrological controls on the large-scale structure, we compared recent geophysical observations in the Shikoku area, southwest Japan with petrological models of the hanging wall mantle wedge. As a result, we found a close relationship between mineral assemblages in the mantle wedge and the characteristics of slow slip behaviour recorded in the Shikoku area: Short-term ETSs take place in the antigorite + olivine stability field and silent long-term slow slip events (SSEs) take place in the antigorite+brucite stability field. Based on observations of natural antigorite serpentinites, we propose a model that the dominant serpentinization reaction in the mantle wedge changes with increasing depth resulting in variable extents of pore fluid pressures along slip planes. The serpentinization reaction in the antigorite+brucite stability field (olivine + H2O → antigorite + brucite) proceeds at the expense of water. This is consistent with moderately elevated pore pressures inferred for long-term SSEs. The existence of weak brucite enhances the development of shear zones oblique to the main foliation. The resultant anastomosing network provides fluid pathways that may help reduce pore pressures on slip planes. In contrast, progress of the serpentinization reaction in the antigorite + olivine stability field (olivine + H2O + SiO2 → antigorite) results in a large amount of residual water that contributes to further increase pore fluid pressures on slip planes of short-term SSEs. Our results imply that understanding of serpentinization reactions and their contributions to fluid networks in mantle wedge is important in constructing quantitative 3-D models for strain evolutions along plate boundaries. © 2014 Elsevier B.V